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101.
Fernando Berton Zanchi Rafael Andrade Caceres Rodrigo Guerino Stabeli Walter Filgueira de Azevedo Jr. 《Journal of molecular modeling》2010,16(3):543-550
Purine nucleoside phosphorylase (PNP) (EC.2.4.2.1) is an enzyme that catalyzes the cleavage of N-ribosidic bonds of the purine
ribonucleosides and 2-deoxyribonucleosides in the presence of inorganic orthophosphate as a second substrate. This enzyme
is involved in purine-salvage pathway and has been proposed as a promising target for design and development of antimalarial
and antibacterial drugs. Recent elucidation of the three-dimensional structure of PNP by X-ray protein crystallography left
open the possibility of structure-based virtual screening initiatives in combination with molecular dynamics simulations focused
on identification of potential new antimalarial drugs. Most of the previously published molecular dynamics simulations of
PNP were carried out on human PNP, a trimeric PNP. The present article describes for the first time molecular dynamics simulations
of hexameric PNP from Plasmodium falciparum (PfPNP). Two systems were simulated in the present work, PfPNP in ligand free form, and in complex with immucillin and sulfate.
Based on the dynamical behavior of both systems the main results related to structural stability and protein-drug interactions
are discussed.
相似文献
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105.
Carvalho AF Pinto MP Grou CP Alencastre IS Fransen M Sá-Miranda C Azevedo JE 《The Journal of biological chemistry》2007,282(43):31267-31272
Protein translocation across the peroxisomal membrane requires the concerted action of numerous peroxins. One central component of this machinery is Pex5p, the cycling receptor for matrix proteins. Pex5p recognizes newly synthesized proteins in the cytosol and promotes their translocation across the peroxisomal membrane. After this translocation step, Pex5p is recycled back into the cytosol to start a new protein transport cycle. Here, we show that mammalian Pex5p is ubiquitinated at the peroxisomal membrane. Two different types of ubiquitination were detected, one of which is thiol-sensitive, involves Cys(11) of Pex5p, and is necessary for the export of the receptor back into the cytosol. Together with mechanistic data recently described for yeast Pex5p, these findings provide strong evidence for the existence of Pex4p- and Pex22p-like proteins in mammals. 相似文献
106.
Ninhaus-Silveira A Foresti F de Azevedo A Agostinho CA Veríssimo-Silveira R 《Zygote (Cambridge, England)》2007,15(3):267-271
The yolk syncytial layer (YSL) has been regarded as one of the main obstacles for a successful cryopreservation of fish embryos. The purpose of this study was to identify and characterize the YSL in Prochilodus lineatus, a fish species found in southeastern Brazil and considered a very important fishery resource. Embryos were obtained through artificial breeding by hormonal induction. After fertilization, the eggs were incubated in vertical incubators with a controlled temperature (28 degrees C). Embryos were collected in several periods of development up to hatching and then fixed with 2% glutaraldehyde and 4% paraformaldehyde in 0.1 M sodium phosphate buffer (pH 7.3). Morphological analyses were carried out under either light, transmission or scanning electron microscopy. The formation of the YSL in P. lineatus embryos starts at the end of the cleavage stage (morula), mainly at the margin of the blastoderm, and develops along the embryo finally covering the entire yolk mass (late gastrula) and producing a distinct intermediate zone between the yolk and the endodermal cells. The YSL was characterized by the presence of microvilli on the contact region with the yolk endoderm. A cytoplasmic mass, full of mitochondria, vacuoles, ribosomes, endomembrane nets and euchromatic nuclei, indicated a high metabolic activity. This layer is shown as an interface between the yolk and the embryo cells that, besides sustaining and separating the yolk, acts as a structure that makes it available for the embryo. The structural analyses identified no possible barriers to cryoprotectant penetration. 相似文献
107.
Bezerra GA Oliveira TM Moreno FB de Souza EP da Rocha BA Benevides RG Delatorre P de Azevedo WF Cavada BS 《Journal of structural biology》2007,160(2):168-176
Plant lectins, especially those purified from species of the Leguminosae family, represent the best studied group of carbohydrate-binding proteins. The legume lectins from Diocleinae subtribe are highly similar proteins that present significant differences in the potency/efficacy of their biological activities. The structural studies of the interactions between lectins and sugars may clarify the origin of the distinct biological activities observed in this high similar class of proteins. In this way, this work presents a crystallographic study of the ConM and CGL (agglutinins from Canavalia maritima and Canavalia gladiata, respectively) in the following complexes: ConM/CGL:Man(alpha1-2)Man(alpha1-O)Me, ConM/CGL:Man(alpha1-3)Man(alpha1-O)Me and ConM/CGL:Man(alpha1-4)Man(alpha1-O)Me, which crystallized in different conditions and space group from the native proteins. The structures were solved by molecular replacement, presenting satisfactory values for R(factor) and R(free). Comparisons between ConM, CGL and ConA (Canavalia ensiformis lectin) binding mode with the dimannosides in subject, presented different interactions patterns, which may account for a structural explanation of the distincts biological properties observed in the lectins of Diocleinae subtribe. 相似文献
108.
Louisy Sanches dos Santos Camila Azevedo Antunes Cintia Silva dos Santos José Augusto Adler Pereira Priscila Soares Sabbadini Maria das Gra?as de Luna Vasco Azevedo Raphael Hirata Júnior Andreas Burkovski Lídia Maria Buarque de Oliveira Asad Ana Luíza Mattos-Guaraldi 《Memórias do Instituto Oswaldo Cruz》2015,110(5):662-668
Corynebacterium diphtheriae, the aetiologic agent of diphtheria,
also represents a global medical challenge because of the existence of invasive
strains as causative agents of systemic infections. Although tellurite
(TeO32-) is toxic to most microorganisms, TeO32--resistant
bacteria, including C. diphtheriae, exist in
nature. The presence of TeO32--resistance (TeR)
determinants in pathogenic bacteria might provide selective advantages in the natural
environment. In the present study, we investigated the role of the putative
TeR determinant (CDCE8392_813gene) in the virulence
attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in
the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen
species (hydrogen peroxide), but not to other antimicrobial agents. The LDCIC-L1
mutant also showed a decrease in both the lethality of Caenorhabditis elegans
and the survival inside of human epithelial cells compared to wild-type
strain. Conversely, the haemagglutinating activity and adherence to and formation of
biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813
gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and
pathogenic potential of C. diphtheriae. 相似文献
109.
Analice C. Azevedo Cláudia B. P. Bento Jeronimo C. Ruiz Marisa V. Queiroz Hilário C. Mantovani 《Applied and environmental microbiology》2015,81(20):7290-7304
Some species of ruminal bacteria are known to produce antimicrobial peptides, but the screening procedures have mostly been based on in vitro assays using standardized methods. Recent sequencing efforts have made available the genome sequences of hundreds of ruminal microorganisms. In this work, we performed genome mining of the complete and partial genome sequences of 224 ruminal bacteria and 5 ruminal archaea to determine the distribution and diversity of bacteriocin gene clusters. A total of 46 bacteriocin gene clusters were identified in 33 strains of ruminal bacteria. Twenty gene clusters were related to lanthipeptide biosynthesis, while 11 gene clusters were associated with sactipeptide production, 7 gene clusters were associated with class II bacteriocin production, and 8 gene clusters were associated with class III bacteriocin production. The frequency of strains whose genomes encode putative antimicrobial peptide precursors was 14.4%. Clusters related to the production of sactipeptides were identified for the first time among ruminal bacteria. BLAST analysis indicated that the majority of the gene clusters (88%) encoding putative lanthipeptides contained all the essential genes required for lanthipeptide biosynthesis. Most strains of Streptococcus (66.6%) harbored complete lanthipeptide gene clusters, in addition to an open reading frame encoding a putative class II bacteriocin. Albusin B-like proteins were found in 100% of the Ruminococcus albus strains screened in this study. The in silico analysis provided evidence of novel biosynthetic gene clusters in bacterial species not previously related to bacteriocin production, suggesting that the rumen microbiota represents an underexplored source of antimicrobial peptides. 相似文献